Fig. 2

Neuronal TNFR1 promotes microglial responses, OLG loss, and axon damage in CPZ demyelination. (Ai) LFB staining of myelin (arrowheads showing maintenance of myelin at CPZ3 in nTNFR1KO mice), (Bi) CNPase immunostaining of myelin and OLG (arrowheads and inset showing maintenance of myelin and OLG at CPZ5 in nTNFR1KO mice), (Ci) Iba1 immunostaining of microglia, and (Di) APP immunostaining of axonal spheroids (inset showing higher magnification) in serial brain coronal paraffin sections through the medial corpus callosum from representative nTNFR1KO and TNFR1ff control naïve (CPZ0) or CPZ-fed CPZ3 and CPZ5 mice. Scale bars: 500 μM (Ai), and 100 μM (Bi, Ci, Di). (Aii) Semiquantitative scoring of demyelination (loss of LFB staining) in the medial corpus callosum of the same groups of mice represented in Ai. Quantitative representation of (Bii) CNPase immunoreactivity by densitometry, (Cii) Iba1 immunoreactivity by % area covered, and (Dii) numbers of APP immunoreactive spheroids/mm2 tissue in the corpus callosum of groups of mice represented in Bi, Ci, and Di, respectively. Results shown in Bii and Dii are normalized against values in CPZ0 mice of each genotype (n = 2 for all CPZ0 and control CPZ6+2, and n ≥ 7 mice for other time points). Results are from two independent experiments. The most relevant statistically significant differences after comparisons between groups are shown by two-way ANOVA with Bonferroni’s test (*), and pairwise comparisons by Student’s t-test (#). *, #p ≤ 0.05, **p ≤ 0.005, ***p ≤ 0.001